Found 10359 publications. Showing page 351 of 415:
2022
Acquired drug resistance and metastasis in breast cancer (BC) are coupled with epigenetic deregulation of gene expression. Epigenetic drugs, aiming to reverse these aberrant transcriptional patterns and sensitize cancer cells to other therapies, provide a new treatment strategy for drug-resistant tumors. Here we investigated the ability of DNA methyltransferase (DNMT) inhibitor decitabine (DAC) to increase the sensitivity of BC cells to anthracycline antibiotic doxorubicin (DOX). Three cell lines representing different molecular BC subtypes, JIMT-1, MDA-MB-231 and T-47D, were used to evaluate the synergy of sequential DAC + DOX treatment in vitro. The cytotoxicity, genotoxicity, apoptosis, and migration capacity were tested in 2D and 3D cultures. Moreover, genome-wide DNA methylation and transcriptomic analyses were employed to understand the differences underlying DAC responsiveness. The ability of DAC to sensitize trastuzumab-resistant HER2-positive JIMT-1 cells to DOX was examined in vivo in an orthotopic xenograft mouse model. DAC and DOX synergistic effect was identified in all tested cell lines, with JIMT-1 cells being most sensitive to DAC. Based on the whole-genome data, we assume that the aggressive behavior of JIMT-1 cells can be related to the enrichment of epithelial-to-mesenchymal transition and stemness-associated pathways in this cell line. The four-week DAC + DOX sequential administration significantly reduced the tumor growth, DNMT1 expression, and global DNA methylation in xenograft tissues. The efficacy of combination therapy was comparable to effect of pegylated liposomal DOX, used exclusively for the treatment of metastatic BC. This work demonstrates the potential of epigenetic drugs to modulate cancer cells' sensitivity to other forms of anticancer therapy.
2022
A pooled analysis of molecular epidemiological studies on modulation of DNA repair by host factors
Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual’s ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which run population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair, no overall effect of age was found, but sex differences were most pronounced in the oldest quartile (>61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m2 was related to higher levels of BER. However, when BMI exceeded 35 kg/m2, repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies.
2022
2022
Emission inventories indicate that thallium, a highly toxic metal, is emitted during coal burning and cement production. These estimates have been established only for the 1980s and 1990s but up to now they have not been compared to long-term observations. Here we used alpine ice cores to document thallium pollution over Europe since ∼1850. Ice-core thallium concentrations increased from 1890 to 1910, and decreased after 1965 to concentrations that were half 1890 levels. Comparison of ice-core trends, estimated past emissions, and state-of-the-art atmospheric aerosol transport modeling suggest that coal burning was responsible for thallium pollution in Europe, particularly from 1920 to 1965 because of high coal consumption at that time. The subsequent decline resulted from decreased coal consumption and reduced emissions following technological improvements. The ice-core data suggest that the rapid growth of cement production that took place in Europe after 1950 had a limited impact on thallium pollution.
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Microplastics in Norwegian coastal areas, rivers, lakes and air (MIKRONOR1)
Norsk institutt for vannforskning
2022
The EmSite model for high resolution emissions from machinery in construction sites
The report describes the EmSite model developed to estimate exhaust and non-exhaust emissions from non-road mobile
machinery (NRMM) used in building and construction. The model is based on a complete national database of the exact
location of construction and building activity, machine registries and variables that affect emissions (ground conditions, meteorology, type of ground material). EmSite model allows us to determine, i) the location, area and time of construction projects at fine resolution; ii) energy demand for NRMM; and iii) fuel consumption, air pollutants and GHGs emissions. For exhaust emissions, specific dynamic emission factors for NRMMs were developed. For non-exhaust emissions, an approach based on the Tier 1 (EMEP/EEA Guidebook, 2019) was chosen. EmSite allows for bottom-up estimates for NRMM employed in construction, and the results are comparable with official air pollutant and GHGs emissions.
NILU
2022
Screening of Chlorinated Paraffins, Dechloranes and UV-filters in Nordic Countries
In 2019, the Nordic screening group decided to perform a Nordic screening on chlorinated paraffins, dechloranes and UV-filters. These compounds are used in a wide range of applications. They all have long range transport characteristics and can potentially be regulated under the Stockholm POP convention. However, there are still huge data gaps, which need to be addressed in order to fulfill regulation requests. Several topics and questions were in focus for more measurements and a deeper understanding: (1) importance of long-range atmospheric transport and deposition, (2) differences/similarities in terrestrial versus marine food chains, and (3) variations between the Nordic countries and between urban and remote areas. Based on these priorities, availability of samples, and other practical reasons, samples from different Nordic countries, different environments, and both urban and remote places were selected. This study includes analysis of the compounds in air, marine and freshwater fish and marine mammals and bird eggs, but as the chlorinated paraffins also have been found to accumulate in the terrestrial food web, terrestrial mammals and bird eggs were included as well. Additionally, samples of pine needles were analysed both to look at the possibility for long range transport and to investigate it as a possible source of chlorinated paraffins for the terrestrial mammals.
Nordic Council of Ministers
2022
Do Carbon Nanotubes and Asbestos Fibers Exhibit Common Toxicity Mechanisms?
During the last two decades several nanoscale materials were engineered for industrial and medical applications. Among them carbon nanotubes (CNTs) are the most exploited nanomaterials with global production of around 1000 tons/year. Besides several commercial benefits of CNTs, the fiber-like structures and their bio-persistency in lung tissues raise serious concerns about the possible adverse human health effects resembling those of asbestos fibers. In this review, we present a comparative analysis between CNTs and asbestos fibers using the following four parameters: (1) fibrous needle-like shape, (2) bio-persistent nature, (3) high surface to volume ratio and (4) capacity to adsorb toxicants/pollutants on the surface. We also compare mechanisms underlying the toxicity caused by certain diameters and lengths of CNTs and asbestos fibers using downstream pathways associated with altered gene expression data from both asbestos and CNT exposure. Our results suggest that indeed certain types of CNTs are emulating asbestos fiber as far as associated toxicity is concerned.
2022
Evaluation and Global-Scale Observation of Nitrous Oxide from IASI on Metop-A
Nitrous oxide (N2O) is a greenhouse gas difficult to estimate by satellite because of its weak spectral signature in the infra-red band and its low variability in the troposphere. Nevertheless, this study presents the evaluation of new tropospheric N2O observations from the Infrared Atmospheric Sounder Interferometer (IASI) on Metop-A using the Toulouse N2O Retrieval Version 2.0 tool. This tool is based on the Radiative Transfer for Tiros Operational Vertical sounder (RTTOV) model version 12.3 coupled to the Levenberg-Marquardt optimal estimation method enabling the simultaneous retrieval of methane, water vapour, temperature profiles together with surface temperature and emissivity within the 1240–1350 cm−1 window. In this study, we focused on the upper troposphere (300 hPa) where the sensitivity of IASI is significant. The IASI N2O data has been evaluated using aircraft N2O observations from the High-performance Instrumented Airborne Platform for Environmental Research Pole-to-Pole Observations (HIPPO) campaigns in 2009, 2010, and 2011 and from the National Oceanic and Atmospheric Administration’s (NOAA) Global Greenhouse Gas Reference Network (GGGRN) in 2011. In addition, we evaluated the IASI N2O using ground-based N2O measurements from 9 stations belonging to the Network for the Detection of Atmospheric Composition Change (NDACC). We found a total random error of ∼2 ppbv (0.6%) for one single retrieval at 300 hPa. Under favorable conditions, this error is also found in the vertical level pressure range 300–500 hPa. It decreases rapidly to ∼0.4 ppbv (0.1%) when we average on a 1° × 1° box. In addition, independent observations allows the estimation of bias with the IASI TN2OR v2.0 N2O. The bias between IASI and aircraft N2O data at 300 hPa is ∼1.0 ppbv (∼0.3%). We found an estimated random error of ∼2.3 ppbv (∼0.75%). This study also shows relatively high correlations between IASI data and aircraft in situ profiles but more varying correlations over the year 2011 depending on the location between IASI and NDACC remote sensing data. Finally, we present daily, monthly, and seasonal IASI N2O horizontal distributions in the upper troposphere as well as cross sections for different seasons that exhibit maxima in the Tropical band especially over Africa and South America.
2022
Here we provide an overview of the newly commenced project ‘ReGAME - Reliable Global Methane Emissions estimates in a changing world’, funded by Research Council of Norway from 2021-2025, where we combine new developments in atmospheric methane observations: isotopic ratios (deuterium and 13C in methane), and the Integrated Carbon Observation System (ICOS) ground-based station network with atmospheric models (the chemistry transport model OsloCTM, and inversion model FLEXINVERT) to understand how and why atmospheric methane levels are increasing. The project has a particular focus on understanding the state of Arctic methane reservoirs such as ocean seeps and high latitude wetlands. This includes plans for a new observing system aboard the ice breaking vessel RV Kronprins Haakon and ocean observations, e.g., dynamics of Seep fluxes assessed during 1 year of continuous measurements at a seep site the NorEMSO project, updated information on spatial seep distribution via echo sounding, as well as high resolution high-latitude inversion modeling of atmospheric methane with FLEXINVERT. Furthermore, we investigate the utility of including of satellite data (TROPOMI aboard the Sentinel 5P mission) together with ground-based data, in inversion modeling. The inclusion of satellite data into inversion models is quite novel and offers rewards by increasing spatial coverage compared to ground based networks alone, potentially reducing uncertainties in the model outputs, and challenges due to satellite data uncertainties, spatial/ temporal coverage, and handling large data fields
2022
Impact of the Pacific sector sea ice loss on the sudden stratospheric warming characteristics
The atmospheric response to Arctic sea ice loss remains a subject of much debate. Most studies have focused on the sea ice retreat in the Barents-Kara Seas and its troposphere-stratosphere influence. Here, we investigate the impact of large sea ice loss over the Chukchi-Bering Seas on the sudden stratospheric warming (SSW) phenomenon during the easterly phase of the Quasi-Biennial Oscillation through idealized large-ensemble experiments based on a global atmospheric model with a well-resolved stratosphere. Although culminating in autumn, the prescribed sea ice loss induces near-surface warming that persists into winter and deepens as the SSW develops. The resulting temperature contrasts foster a deep cyclonic circulation over the North Pacific, which elicits a strong upward wavenumber-2 activity into the stratosphere, reinforcing the climatological planetary wave pattern. While not affecting the SSW occurrence frequency, the amplified wave forcing in the stratosphere significantly increases the SSW duration and intensity, enhancing cold air outbreaks over the continents afterward.
2022
Comparison of particle number size distribution trends in ground measurements and climate models
Despite a large number of studies, out of all drivers of radiative forcing, the effect of aerosols has the largest uncertainty in global climate model radiative forcing estimates. There have been studies of aerosol optical properties in climate models, but the effects of particle number size distribution need a more thorough inspection. We investigated the trends and seasonality of particle number concentrations in nucleation, Aitken, and accumulation modes at 21 measurement sites in Europe and the Arctic. For 13 of those sites, with longer measurement time series, we compared the field observations with the results from five climate models, namely EC-Earth3, ECHAM-M7, ECHAM-SALSA, NorESM1.2, and UKESM1. This is the first extensive comparison of detailed aerosol size distribution trends between in situ observations from Europe and five earth system models (ESMs). We found that the trends of particle number concentrations were mostly consistent and decreasing in both measurements and models. However, for many sites, climate models showed weaker decreasing trends than the measurements. Seasonal variability in measured number concentrations, quantified by the ratio between maximum and minimum monthly number concentration, was typically stronger at northern measurement sites compared to other locations. Models had large differences in their seasonal representation, and they can be roughly divided into two categories: for EC-Earth and NorESM, the seasonal cycle was relatively similar for all sites, and for other models the pattern of seasonality varied between northern and southern sites. In addition, the variability in concentrations across sites varied between models, some having relatively similar concentrations for all sites, whereas others showed clear differences in concentrations between remote and urban sites. To conclude, although all of the model simulations had identical input data to describe anthropogenic mass emissions, trends in differently sized particles vary among the models due to assumptions in emission sizes and differences in how models treat size-dependent aerosol processes. The inter-model variability was largest in the accumulation mode, i.e. sizes which have implications for aerosol–cloud interactions. Our analysis also indicates that between models there is a large variation in efficiency of long-range transportation of aerosols to remote locations. The differences in model results are most likely due to the more complex effect of different processes instead of one specific feature (e.g. the representation of aerosol or emission size distributions). Hence, a more detailed characterization of microphysical processes and deposition processes affecting the long-range transport is needed to understand the model variability.
2022
Using the example of sulfur hexafluoride (SF6), we investigate the use of Lagrangian particle dispersion models (LPDMs) for inverse modeling of greenhouse gas (GHG) emissions and explore the limitations of this approach. We put the main focus on the impacts of baseline methods and the LPDM backward simulation period on the a posteriori emissions determined by the inversion. We consider baseline methods that are based on a statistical selection of observations at individual measurement sites and a global-distribution-based (GDB) approach, where global mixing ratio fields are coupled to the LPDM back-trajectories at their termination points. We show that purely statistical baseline methods can cause large systematic errors, which lead to inversion results that are sensitive to the LPDM backward simulation period and can generate unrealistic global total a posteriori emissions. The GDB method produces a posteriori emissions that are far less sensitive to the backward simulation period and that show a better agreement with recognized global total emissions. Our results show that longer backward simulation periods, beyond the often used 5 to 10 d, reduce the mean squared error and increase the correlation between a priori modeled and observed mixing ratios. Also, the inversion becomes less sensitive to biases in the a priori emissions and the global mixing ratio fields for longer backward simulation periods. Further, longer periods might help to better constrain emissions in regions poorly covered by the global SF6 monitoring network. We find that the inclusion of existing flask measurements in the inversion helps to further close these gaps and suggest that a few additional and well-placed flask sampling sites would have great value for improving global a posteriori emission fields.
2022